PMID- 22566640
OWN - NLM
STAT- MEDLINE
DCOM- 20120827
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 23
DP  - 2012 Jun 5
TI  - MHC class II distribution in dendritic cells and B cells is determined by 
      ubiquitin chain length.
PG  - 8820-7
LID - 10.1073/pnas.1202977109 [doi]
AB  - Dendritic cells (DCs) and B cells present antigen-derived peptides bound to MHC 
      class II (MHC II) molecules for recognition by CD4-positive T lymphocytes. DCs 
      control the intracellular traffic of peptide-MHC II complexes by regulating the 
      ubiquitination of MHC II. In resting or "immature" DCs, ubiquitinated MHC II 
      molecules are targeted to lysosomes, but upon pathogen-induced "maturation," 
      ubiquitination is down-regulated and MHC II can accumulate on the plasma membrane 
      of mature DCs. Although B cells constitutively ubiquitinate their MHC II, it 
      unexpectedly remains at the surface. We find that DCs and B cells differ in MHC 
      II-conjugated ubiquitin (Ub) chain length: four to six Ub in immature DCs vs. two 
      to three in B cells. In both cell types, experimentally increasing Ub chain 
      length led to efficient lysosomal transport of MHC II, whereas MHC II with fewer 
      than two Ubs did not reach lysosomes. Thus, Ub chain length plays a crucial role 
      in regulating the intracellular fate and function of MHC II in DCs and B cells.
FAU - Ma, Jessica K
AU  - Ma JK
AD  - Department of Cell Biology, Yale University School of Medicine, New Haven, CT 
      06520, USA.
FAU - Platt, Mia Y
AU  - Platt MY
FAU - Eastham-Anderson, Jeffrey
AU  - Eastham-Anderson J
FAU - Shin, Jeoung-Sook
AU  - Shin JS
FAU - Mellman, Ira
AU  - Mellman I
LA  - eng
PT  - Journal Article
DEP - 20120507
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Antigens)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Ubiquitin)
RN  - 0 (epsin)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport/metabolism
MH  - Animals
MH  - Antigens/immunology/*metabolism
MH  - B-Lymphocytes/immunology/*metabolism
MH  - Blotting, Western
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Cell Line
MH  - Dendritic Cells/immunology/*metabolism
MH  - Endocytosis/physiology
MH  - Flow Cytometry
MH  - Genes, MHC Class II/*genetics
MH  - Immunoprecipitation
MH  - Mice
MH  - Multiprotein Complexes/genetics/immunology/*metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Ubiquitin/*metabolism
PMC - PMC3384207
COIS- The authors declare no conflict of interest.
EDAT- 2012/05/09 06:00
MHDA- 2012/08/28 06:00
PMCR- 2012/12/05
CRDT- 2012/05/09 06:00
PHST- 2012/05/09 06:00 [entrez]
PHST- 2012/05/09 06:00 [pubmed]
PHST- 2012/08/28 06:00 [medline]
PHST- 2012/12/05 00:00 [pmc-release]
AID - 1202977109 [pii]
AID - 201202977 [pii]
AID - 10.1073/pnas.1202977109 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):8820-7. doi: 
      10.1073/pnas.1202977109. Epub 2012 May 7.